Infectious SIV/HIV chimera viruses (SHIV) may play a crucial role in HIV-1 vaccine development. There are no ideal animal models to test HIV-1 vaccines, primarily because HIV-1 has not caused disease in nonhuman primates. Historically, vaccine efficacy is defined by whether the host's immunological response to the vaccine blocks disease development after infectious challenge. However, without disease as an end point we are left to consider the infection-blocking effect of the vaccine (so-called sterilizing immunity). To date, HIV-1 vaccine efficacy studies have had to rely on the latter as a predictor of effectiveness, but there is no strong evidence that sterilizing immunity will be required to block AIDS disease following HIV infection. Briefly described, SHIV viruses are SIV enclosed in an HIV envelope. The logic that led to the development of SHIV has two principal components 1) most candidate HIV-1 vaccines include env-derived antigen and since the virus envelope is essential during initial infection events, antibodies to the envelope following vaccination may limit or block infection; and 2) the SIV portions of SHIV may retain viral pathogenicity in macaques, thus restoring the potential for a disease end point during vaccine challenge studies. In the current study, we have determined the macaque infectious dose (MID) of SHIVIIIB in Macaca nemestrina and have used that value to prepare a viral challenge dose for HIV-vaccinated animals to assess the efficacy of the vaccine in macaques. The MID was determined to be between 0.1 and 1.0 TCID50. The animals were monitored to determine the pathogenicity of SHIVIIIB in M. nemestrina. Although there are only 9 survivors, none of these animals progressed to AIDS during 2 years of observation. The same stock had been titered in M. mulatta at another institute resulting in an MID of 1 TCID50. In contrast to our results, in which virus was readily recovered for up to 1 year, the M. mulatta became virus negative at 16 weeks.